NEW YORK – Proteomics firm Alamar Biosciences is seeing strong interest in its neurology immunoassay panel as a tool for Alzheimer's research, company officials said.

纽约——蛋白质组学公司阿拉玛生物科学公司（AlamarBiosciences）的官员表示，该公司对其神经病学免疫分析小组作为阿尔茨海默氏病研究的工具抱有浓厚兴趣。

The panel, called the NULISAseq CNS Disease Panel 120, measures 120 proteins linked to neurological disease, and is proving a particularly attractive option for scientists and clinicians studying biomarkers and pathways outside the brain amyloid paradigm where much Alzheimer's research has concentrated, said Yuling Luo, Alamar's founder, chairman, and CEO..

Alamar的创始人、董事长兼首席执行官罗玉玲（Yuling Luo）表示，该小组被称为NULISAseq中枢神经系统疾病小组120，可测量120种与神经系统疾病相关的蛋白质，对于研究大脑淀粉样蛋白范式以外的生物标志物和通路的科学家和临床医生来说，这是一个特别有吸引力的选择，而大脑淀粉样蛋白范式是阿尔茨海默病研究的重点。。

Existing Alzheimer's drugs as well as the biomarkers commonly used for diagnosis, all focus on targeting or detecting the brain amyloid plaques characteristic of the disease. Traditionally, PET imaging and cerebrospinal fluid (CSF) testing have been used to detect amyloid plaques. More recently, blood-based biomarkers — phosphorylated-tau 217 in particular — have shown great promise for this purpose..

现有的阿尔茨海默病药物以及常用于诊断的生物标志物都专注于靶向或检测该疾病的脑淀粉样斑块特征。传统上，PET成像和脑脊液（CSF）检测已被用于检测淀粉样斑块。最近，基于血液的生物标志物（特别是磷酸化的tau 217）在这方面显示出巨大的前景。。

Researchers are aware, however, that amyloid pathology is only one aspect of Alzheimer's, with changes across a variety of biological pathways contributing to the development and progression of the disease.

然而，研究人员意识到，淀粉样蛋白病理学只是阿尔茨海默氏病的一个方面，各种生物学途径的变化有助于疾病的发展和进展。

The general consensus among key opinion leaders is that Alzheimer's disease is highly heterogeneous, Luo said. 'That heterogeneity requires an understanding of Alzheimer's disease at the molecular level beyond p-tau 217,' he noted.

罗说，关键意见领袖的普遍共识是，阿尔茨海默病是高度异质性的他指出，这种异质性需要在p-tau 217以外的分子水平上了解阿尔茨海默病。

Studying large numbers of proteins linked to neurological conditions like Alzheimer's can be challenging, however, particularly given that they are often present in blood at low concentrations, requiring highly sensitive assays. CSF samples are also an option, but collection of these samples is more difficult as it requires a lumbar puncture..

然而，研究大量与阿尔茨海默氏病等神经系统疾病相关的蛋白质可能具有挑战性，特别是考虑到它们通常以低浓度存在于血液中，需要高度敏感的检测。脑脊液样本也是一种选择，但这些样本的收集更加困难，因为它需要进行腰椎穿刺。。

Researchers use tools like mass spectrometry and affinity-based assay panels from companies like Olink and Standard BioTools for broader discovery experiments in Alzheimer's, but Luo said Alamar believes its NULISA (NUcleic acid-Linked Immuno-Sandwich Assay) technology offers advantages in sensitivity and ease of use that will help it win customers in this space..

研究人员使用来自Olink和Standard BioTools等公司的质谱和基于亲和力的检测面板等工具进行更广泛的阿尔茨海默氏病发现实验，但Luo表示，Alamar相信其NULISA（核酸连接免疫夹心检测）技术在灵敏度和易用性方面具有优势，将有助于在这一领域赢得客户。。

NULISA is based on the proximity ligation assay (PLA) originally commercialized by Olink Bioscience, the forerunner of Olink. (Olink is currently suing Alamar for patent infringement.) PLA uses pairs of antibodies attached to unique DNA sequences to detect proteins of interest. When the antibodies bind to their targets, the attached DNA strands are brought into proximity and ligated, forming a new template that can then be amplified by rolling circle amplification..

NULISA基于最初由Olink的先驱Olink Bioscience商业化的邻近连接测定（PLA）。（Olink目前正在起诉Alamar侵犯专利。）PLA使用附着在独特DNA序列上的成对抗体来检测感兴趣的蛋白质。当抗体与其靶标结合时，附着的DNA链被接近并连接，形成新的模板，然后可以通过滚环扩增进行扩增。。

PLA has been in widespread use for more than a decade. According to Alamar, NULISA improves upon the standard PLA method by using a two-stage wash and capture workflow that reduces assay background, thereby improving its sensitivity. Alamar has also developed an automated platform for running NULISA assays, its Argo HT instrument, which the company says requires less than 30 minutes of hands-on time per experiment.

解放军已经广泛使用了十多年。据Alamar称，NULISA通过使用两阶段洗涤和捕获工作流程改进了标准PLA方法，该工作流程减少了测定背景，从而提高了其灵敏度。Alamar还开发了一个自动化平台，用于运行其Argo HT仪器NULISA分析，该公司表示，每个实验需要不到30分钟的动手时间。

Traditional PLA experiments can involve several hours or more of hands-on time..

传统的PLA实验可能需要几个小时或更长的动手时间。。

Luo noted that Alamar had not initially planned to make neurology an area of focus but received strong interest from potential customers in the space, especially around the possibility that the platform's high sensitivity could enable detection of a wide range of neurology markers in blood.

罗指出，阿拉玛最初并没有计划将神经病学作为重点领域，但该领域的潜在客户对此产生了浓厚兴趣，特别是该平台的高灵敏度可能会检测血液中的多种神经病学标记。

He said the company built the CNS Disease Panel based on input from these potential customers, with an undisclosed large pharma firm providing an initial list of 75 markers it was interested in measuring and other researchers and academics in the space then suggesting additional proteins of interest..

。。

Thomas Karikari, an assistant professor of psychiatry at the University of Pittsburgh, recently used the panel for an analysis of 176 plasma samples taken from 113 subjects from the MYHAT-NI cohort, detailed in a paper published this month in Molecular Neurodegeneration. The researchers identified 14 proteins that were significantly altered in individuals with brain amyloid pathology as determined by PET imaging.

匹兹堡大学精神病学助理教授托马斯·卡里卡里（ThomasKarikari）最近利用该小组对来自MYHAT-NI队列的113名受试者的176份血浆样本进行了分析，详细内容见本月发表在《分子神经退行性变》上的一篇论文。研究人员通过PET成像确定了14种蛋白质，这些蛋白质在患有脑淀粉样蛋白病理的个体中发生了显着改变。

They also identified three markers that increased longitudinally in amyloid-positive patients as their amyloid pathology worsened, as well as a set of markers linked to functions including 'neuroinflammation, synaptic function, and cerebrovascular integrity' that increased longitudinally with changes in PET tau levels..

他们还确定了淀粉样蛋白阳性患者随着淀粉样蛋白病理恶化而纵向增加的三种标志物，以及一组与功能相关的标志物，包括“神经炎症，突触功能和脑血管完整性”，这些标志物随着PET tau水平的变化而纵向增加。。

'More recently, the [Alzheimer's research] field has become more appreciative of the multifaceted [and] multifactorial nature of Alzheimer's,' Karikari said, noting that this has spurred interest in studying larger panels of markers linked to the disease.

卡里卡里说：“最近，阿尔茨海默氏病研究领域越来越重视阿尔茨海默氏病的多方面和多因素性质，并指出这激发了人们对研究与该病相关的更多标记的兴趣。

He said his lab found the Alamar panel attractive in that it is more comprehensive and sensitive than many other targeted neurology panels, allowing for the measurement of both core markers like forms of amyloid-beta (Aβ) and tau and emerging markers, many of which, he noted, were previously accessible only in CSF..

他说，他的实验室发现Alamar小组很有吸引力，因为它比许多其他靶向神经病学小组更全面和敏感，可以测量淀粉样蛋白β（Aβ）和tau等核心标志物以及新兴标志物，他指出，其中许多标志物以前只能在脑脊液中获得。。

Karikari said that he and his colleagues consider their recent study to be a proof of concept demonstrating the ability of the Alamar technology to measure these markers in blood. Next, he said, they hope to begin testing certain of these markers — particularly those linked to inflammation and vascular dysfunction — in other well-characterized patient cohorts to determine what information they might provide about the development and progression of Alzheimer's..

卡里卡里说，他和他的同事认为他们最近的研究是一个概念验证，证明了阿拉玛技术能够测量血液中的这些标记。接下来，他说，他们希望在其他特征明确的患者队列中开始测试某些标记物，特别是与炎症和血管功能障碍有关的标记物，以确定他们可能提供的有关阿尔茨海默氏病发展和进展的信息。。

While Alamar's NULISA assays and the Argo HT instrument are for research use only, the company has clinical ambitions. Luo said it plans to develop a clinical platform, the Argo Dx, that Alamar and outside parties could use to develop and run diagnostics using its technology. He declined to give a timeline for when the company will launch such a system but said it hopes to do so 'as soon as we can.'.

虽然Alamar的NULISA分析和Argo HT仪器仅用于研究用途，但该公司有临床雄心。罗说，它计划开发一个临床平台Argo Dx，Alamar和外部各方可以使用它的技术开发和运行诊断。他拒绝给出该公司何时推出此类系统的时间表，但表示希望“尽快”推出。

In the Molecular Neurodegeneration study, Karikari and his coauthors looked at the performance of Alamar's assays for measuring a set of plasma proteins currently used in Alzheimer's diagnoses including p-tau 217, p-tau 231, p-tau 181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), Aβ40, and Aβ42.

在分子神经变性研究中，Karikari和他的合著者研究了Alamar测定法的性能，该测定法用于测量目前用于阿尔茨海默病诊断的一组血浆蛋白，包括p-tau 217，p-tau 231，p-tau 181，神经丝轻（NfL），胶质原纤维酸性蛋白（GFAP），aβ40和aβ42。

They compared the values for these markers produced by the Argo HT to values produced by assays run using Quanterix's Simoa technology, which is widely used in Alzheimer's research as well as for clinical testing..

他们将Argo-HT产生的这些标记物的值与使用Quanterix的Simoa技术进行的测定产生的值进行了比较，该技术广泛用于阿尔茨海默氏病的研究以及临床测试。。

They found the two platforms had equivalent diagnostic accuracy in terms of identifying individuals positive for brain amyloid pathology as determined by PET imaging, with both scoring as more than 90 percent accurate once the risk factors of age, APOE4 carrier status, and sex were included.

他们发现，这两个平台在识别PET成像确定的脑淀粉样蛋白病理阳性个体方面具有同等的诊断准确性，一旦包括年龄，APOE4携带者状态和性别等危险因素，两者的准确率均超过90%。

The correlation between the two platforms varied across the seven markers analyzed, with Spearman rank correlation coefficient (rho) values ranging from a high of 0.88 for p-tau 217 to a low of 0.32 for Aβ40.

两个平台之间的相关性在所分析的七个标记中有所不同，Spearman等级相关系数（rho）值范围从p-tau 217的高0.88到aβ40的低0.32。

Karikari said he and his colleagues are now comparing the performance of a variety of platforms for measuring common clinically used blood biomarkers for Alzheimer's. The systems they are looking at include Alamar's NULISA, Quanterix's Simoa, and Fujiebio's Lumipulse G pTau 217/β-Amyloid 1-42 Plasma Ratio in vitro diagnostic test, which the company recently submitted to the US Food and Drug Administration..

Karikari说，他和他的同事现在正在比较各种平台的性能，以测量临床上常用的阿尔茨海默氏病血液生物标志物。他们正在研究的系统包括Alamar的NULISA，Quanterix的Simoa和Fujiebio的Lumipulse G pTau 217/β-淀粉样蛋白1-42血浆比体外诊断测试，该公司最近向美国食品和药物管理局提交了该测试。。

Researchers within the European Predictom project are also using NULISA for Alzheimer's biomarker work. Led by Norway's Stavanger University Hospital, the $22.7 million effort comprises 30 academic and industry partners including Novo Nordisk, GE HealthCare, Siemens Healthineers, the University of Geneva, Kings College London, and Alzheimer Europe, and aims to develop tools for the early detection of Alzheimer's disease..

欧洲Predictom项目的研究人员也在使用NULISA进行阿尔茨海默氏病的生物标志物研究。由挪威斯塔万格大学医院领导，这项耗资2270万美元的工作包括30个学术和行业合作伙伴，包括诺和诺德、通用电气医疗保健公司、西门子医疗保健公司、日内瓦大学、伦敦国王学院和阿尔茨海默氏病欧洲，旨在开发早期发现阿尔茨海默氏病的工具。。

One project within the initiative is looking at whether blood-based Alzheimer's markers can be measured in self-collected finger-prick samples. Led by Nicholas Ashton, associate professor of neurochemistry at the University of Gothenburg, the study aims to measure p-tau 217 in around 4,000 participants using the NULISA assay.

该倡议中的一个项目是研究是否可以在自我收集的手指刺痛样本中测量基于血液的阿尔茨海默氏病标志物。由哥德堡大学神经化学副教授尼古拉斯·阿什顿（NicholasAshton）领导的这项研究旨在使用NULISA分析法测量约4000名参与者的p-tau 217。

The researchers will also measure the full 120 proteins in the CNS Disease Panel in each blood spot..

研究人员还将测量每个血斑中枢神经系统疾病小组中的全部120种蛋白质。。